Dysregulation of interleukin-8 is involved in the onset and relapse of schizophrenia: An independent validation and meta-analysis.

As a major mental health disorder, symptoms of schizophrenia (SCZ) include delusions, reduced motivation, hallucinations, reduced motivation and a variety of cognitive disabilities. Many of these symptoms are now known to be associated with abnormal regulation of the immune system. Low blood levels of cytokines and chemokines have been suggested to be one of the underlying causes of SCZ. However, their biological roles at different stages of SCZ remain unclear. Our objective was to investigate expression patterns of cytokines and chemokines at different stages of onset and relapse in SCZ patients and to conduct an analysis of their relationship to disease progression. We also aimed to identify immune features associated with different disease trajectories in patients with SCZ. Gene set enrichment analysis (GSEA) was used to interrogate the GSE27383 dataset and identify key genes associated with inflammation. These results led us to recruit 36 healthy controls, 40 patients with first-episode psychosis (FEP), and 39 patients with SCZ relapse. Meso Scale Discovery technology was used to independently validate serum levels of 35 cytokines and chemokines. This was followed by a meta-analysis to gain a more comprehensive understanding of the role of interleukin-8 (IL-8/CXCL8) in SCZ. Analysis of the GSE27383 database revealed 3596 genes with distinct expression patterns. A significant portion of these genes were identified as inflammation-related and showed remarkable enrichment in three key pathways: IL-17, cytokine-cytokine receptor, and AGE-RAGE signaling in diabetic complications. We observed co-expression of CXCL8 and IL-16 within these three pathways. In a subsequent analysis of independently validated samples, a notable discrepancy was detected in the inflammatory status between individuals experiencing FEP and those in relapse. In particular, expression of CXCL8 demonstrated superior predictive capability in FEP and relapsed patients. Notably, results of the meta-analysis confirmed that Chinese and European populations were consistent with the overall results (Z = 4.60, P < 0.001; Z = 3.70, P < 0.001). However, in the American subgroup, there was no significant difference in CXCL8 levels between patients with SCZ compared to healthy controls (Z = 1.09, P = 0.277). Our findings suggest that the inflammatory response in patients with SCZ differs across the different stages, with CXCL8 emerging as a potential predictive factor. Collectively, our data suggest that CXCL8 has the potential to serve as a significant immunological signature of SCZ subtypes. Trial registration: The clinical registration number for this trial is ChiCTR2100045240 (Registration Date: 2021/04/09).

A stronger association of mental disorders with smaller particulate matter and a modifying effect of air temperature.

Mental disorders (MDs) can be triggered by adverse weather conditions and particulate matter (PM) such as PM2.5 and PM10 (aerodynamic diameter ≤2.5 µm and ≤10 µm). However, there is a dearth of evidence on the role of smaller PM (e.g. PM1, aerodynamic diameter ≤1 µm) and the potential modifying effects of weather conditions. We aimed to collect daily data on emergency department visits and hospitalisations for schizophrenia-, mood-, and stress-related disorders in a densely populated Chinese city (Hefei) between 2016 and 2019. A time-stratified case-crossover analysis was used to examine the short-term association of MDs with PM1, PM2.5, and PM10. The potential modifying effects of air temperature conditions (cold and warm days) were also explored. The three size-fractioned PMs were all associated with an increased risk of MDs; however, the association differed between emergency department visit and hospitalisation. Specifically, PM1 was primarily associated with an increased risk of emergency department visit, whereas PM2.5 was primarily associated with an increased risk of hospitalisation, and PM10 was associated with an increased risk of both emergency department visit and hospitalisation. The PM-MD association appeared to be greatest (although not significant) for PM1 (odds ratio range: 1.014-1.055), followed by PM2.5 (odds ratio range: 1.001-1.009) and PM10 (odds ratio range: 1.001-1.006). Furthermore, the PM-MD association was observed on cold days; notably, the association between PM and schizophrenia-related disorders was significant on both cold and warm days. Our results suggest that the smaller the PM, the greater the risk of MDs, and that the PM-MD association could be determined by air temperature conditions.

Identification of key modules in metabolic syndrome induced by second-generation antipsychotics based on co-expression network analysis.

Background: Second-generation antipsychotics (SGAs) frequently cause metabolic syndrome (MetS), which raises the risk of heart disease, type 2 diabetes, morbid obesity, atherosclerosis, and hypertension. MetS also impairs cognitive function in patients with schizophrenia. However, the fundamental reasons of MetS caused by SGAs are not yet fully understood. Thus, we aimed to identify potential therapeutic targets for MetS induced by SGAs. Methods: The serum biochemical parameters and the RNA-sequencing of peripheral blood mononuclear cells were measured in three groups (healthy controls and patients with schizophrenia with and without MetS taking SGAs). The study of the weighted gene co-expression network was utilized to pinpoint modules that were significantly connected to clinical markers. Results: Statistical analysis showed significant differences in triglyceride and high-density lipoprotein among the three groups. The TNF signaling pathway, TGF-ß signaling pathway, fatty acid metabolism, NF-kappa B signaling pathway, MAPK signaling pathway, and Toll-like receptor signaling pathway were the pathways that were primarily enriched in the two unique co-expression network modules that were found. Finally, five specific genes (TNF, CXCL8, IL1B, TIMP1, and ESR1) associated with metabolism and immunity pathways were identified. Conclusions: This study indicated that SGAs differentially induced MetS of patients with schizophrenia through metabolic and inflammation-related pathways. Therefore, the potential side effects of drugs on inflammatory processes need to be considered when using SGAs for the treatment of schizophrenia.

Intricate role of intestinal microbe and metabolite in schizophrenia.

BACKGROUND: The brain-gut axis has gained increasing attention due to its contribution to the etiology of various central nervous system disorders. This study aims to elucidate the hypothesis that schizophrenia is associated with disturbances in intestinal microflora and imbalance in intestinal metabolites. By exploring the intricate relationship between the gut and the brain, with the goal of offering fresh perspectives and valuable insights into the potential contribution of intestinal microbial and metabolites dysbiosis to the etiology of schizophrenia. METHODS: In this study, we used a 16S ribosomal RNA (16S rRNA) gene sequence-based approach and an untargeted liquid chromatography-mass spectrometry-based metabolic profiling approach to measure the gut microbiome and microbial metabolites from 44 healthy controls, 41 acute patients, and 39 remission patients, to evaluate whether microbial dysbiosis and microbial metabolite biomarkers were linked with the severity of schizophrenic symptoms. RESULTS: Here, we identified 20 dominant disturbances in the gut microbial composition of patients compared with healthy controls, with 3 orders, 4 families, 9 genera, and 4 species. Several unique bacterial taxa associated with schizophrenia severity. Compared with healthy controls, 145 unusual microflora metabolites were detected in the acute and remission groups, which were mainly involved in environmental information processing, metabolism, organismal systems, and human diseases in the Kyoto encyclopedia of genes and genomes pathway. The Sankey diagram showed that 4 abnormal intestinal and 4 anomalous intestinal microbial metabolites were associated with psychiatric clinical symptoms. CONCLUSIONS: These findings suggest a possible interactive influence of the gut microbiota and their metabolites on the pathophysiology of schizophrenia.

Impacts of PM2.5 before and after COVID-19 outbreak on emergency mental disorders: A population-based quasi-experimental and case-crossover study.

The ongoing COVID-19 pandemic is a great challenge to mental health, but fine particulate matter (PM2.5), an increasingly reported risk factor for mental disorders, has been greatly alleviated during the pandemic in many countries. It remains unknown whether COVID-19 outbreak can affect the association between PM2.5 exposure and the risk of mental disorders. This study aimed to investigate the associations of total and cause-specific mental disorders with PM2.5 exposure before and after the COVID-19 outbreak in China. Data on daily emergency department visits (EDVs) and hospitalizations of mental disorders from 2016 to 2021 were obtained from Anhui Mental Health Center for Hefei city. An interrupted time series analysis was used to quantify the impact of COVID-19 outbreak on EDVs and hospitalizations of mental disorders. A time-stratified case-crossover analysis was employed to evaluate the association of mental disorders with PM2.5 exposure before and after the COVID-19 outbreak, especially in the three months following the COVID-19 outbreak. After COVID-19 outbreak, there was an immediate and significant decrease in total mental disorders, including a reduction of 15% (95% CI: 3%-26%) in EDVs and 44% (95% CI: 36%-51%) in hospitalizations. PM2.5 exposure was associated with increased risk of EDVs and hospitalizations for total and cause-specific mental disorders (schizophrenia, schizotypal and delusional disorders; neurotic, stress-related, and somatoform disorders) before COVID-19 outbreak, but this PM2.5-related risk elevation significantly decreased after COVID-19 outbreak, with greater risk reduction at the first month after the outbreak. However, young people (0-45 years) were still vulnerable to PM2.5 exposure after the COVID-19 outbreak. This study first reveals that the risk of PM2.5-related emergency mental disorders decreased after the COVID-19 outbreak in China. The low concentration of PM2.5 might benefit mental health and greater efforts are required to mitigate air pollution in the post-COVID-19 era.

Potential role between inflammatory cytokines and Tie-2 receptor levels and clinical symptoms in patients with first-episode schizophrenia.

BACKGROUND: Schizophrenia (SCZ) is associated with chronic low-grade inflammation, which may be involved in the underlying pathological mechanism of the disease and may influence patient prognosis. We evaluated the differences in serum cytokine and Tie-2 receptor levels between patients with first-episode SCZ and healthy controls and explored the correlation thereof with clinical symptoms. METHODS: Seventy-six participants were recruited for the present study, including 40 patients with first-episode SCZ and 36 healthy controls. Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) scores, demographic data, and blood samples were collected at baseline. A hypersensitive Meso Scale Discovery (MSD) electrochemiluminescence assay system was used to measure cytokine and Tie-2 receptor levels. Spearman's correlation and stepwise linear regression were used to analyze the data. RESULTS: Serum interleukin-1ß and -4 levels were significantly increased, and Tie-2 levels were significantly decreased, in first-episode SCZ patients as compared to healthy controls. IL-1ß levels were positively correlated with total BPRS scores, resistance subscores, and PANSS positive subscores. Furthermore, IL-1ß levels were negatively correlated with Tie-2 receptor expression levels. Stepwise linear regression analysis demonstrated that IL-1ß levels correlated positively with PANSS positive subscores and BPRS total scores. PANSS negative subscores, general psychopathology subscores, and PANSS total scores had positive effects on the Tie-2 receptor. Receiver operating characteristic (ROC) curve analysis showed that IL-1ß and Tie-2 were highly sensitive and specific for predicting first-episode SCZ symptoms and achieving an area under the ROC curve of 0.8361 and 0.6462, respectively. CONCLUSION: Our results showed that patients with first-episode SCZ have low-grade inflammation. IL-1ß and Tie-2 receptors may be important mediators between inflammation and vascular dysfunction in patients with SCZ and may underlie the increased cardiovascular disease in this population. TRIAL REGISTRATION: The clinical trial registration date was 06/11/2018, registration number was chiCTR1800019343.

Correlation between elevated serum interleukin-1ß, interleukin-16 levels and psychiatric symptoms in patients with schizophrenia at different stages.

BACKGROUND: There is increasing evidence that immune dysfunction plays an important role in the pathogenesis of schizophrenia. Meso Scale Discovery (MSD) is bioanalytical method, which can detect serum inflammatory factors in patients. MSD has higher sensitivities, capturing a narrower range of proteins compared to other methods typically used in similar studies. The present study was aimed to explore the correlation between the levels of serum inflammatory factors and psychiatric symptoms in patients with schizophrenia at different stages and investigate a wide panel of inflammatory factors as independent factors for the pathogenesis of schizophrenia. METHODS: We recruited 116 participants, including patients with first-episode schizophrenia (FEG, n = 40), recurrence patients (REG, n = 40) with relapse-episode schizophrenia, and a control group (healthy people, HP, n = 36). Patients are diagnosed according to the DSM -V. The plasma levels of IFN-γ, IL-10, IL-1ß, IL-2, IL-6, TNF-α, CRP, VEGF, IL-15, and IL-16 were tested by the MSD technique. Patient-related data was collected, including sociodemographic data, positive and negative symptom scale (PANSS), and brief psychiatric rating scale (BPRS) and subscale scores. The independent sample T test, χ2 test, Analysis of covariance (ANCOVA), the least significant difference method (LSD), Spearman's correlation test, binary logistic regression analysis and ROC curve analysis were used in this study. RESULTS: There were significant differences in serum IL-1ß (F = 2.37, P = 0.014) and IL-16 (F = 4.40, P < 0.001) levels among the three groups. The level of serum IL-1ß in the first-episode group was significantly higher than in the recurrence group (F = 0.87, P = 0.021) and control group (F = 2.03, P = 0.013), but there was no significant difference between the recurrence group and control group (F = 1.65, P = 0.806). The serum IL-16 levels in the first-episode group (F = 1.18, P < 0.001) and the recurrence group (F = 0.83, P < 0.001) were significantly higher than in the control group, and there was no significant difference between the first-episode group and the recurrence group (F = 1.65, P = 0.61). Serum IL-1ß was negatively correlated with the general psychopathological score (GPS) of PANSS (R=-0.353, P = 0.026). In the recurrence group, serum IL-16 was positively correlated with the negative score (NEG) of the PANSS scale (R = 0.335, P = 0.035) and negatively correlated with the composite score (COM) (R=-0.329, P = 0.038). In the study, IL-16 levels were an independent variable of the onset of schizophrenia both in the first-episode (OR = 1.034, P = 0.002) and recurrence groups (OR = 1.049, P = 0.003). ROC curve analysis showed that the areas under IL-16(FEG) and IL-16(REG) curves were 0.883 (95%CI:0.794-0.942) and 0.887 (95%CI:0.801-0.950). CONCLUSIONS: Serum IL-1ß and IL-16 levels were different between patients with schizophrenia and healthy people. Serum IL-1ß levels in first-episode schizophrenia and serum IL-16 levels in relapsing schizophrenia were correlated with the parts of psychiatric symptoms. The IL-16 level may be an independent factor associating with the onset of schizophrenia.

Automatic Thoughts, Self-Stigma, and Resilience Among Schizophrenia Patients with Metabolic Syndrome: A Cross-Sectional Study.

Purpose: The study aims to clarify the negative psychological state and resilience impairments of schizophrenia (SCZ) with metabolic syndrome (MetS) while evaluating their potential as risk factors. Patients and Methods: We recruited 143 individuals and divided them into three groups. Participants were evaluated using the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAMD)-24, Hamilton Anxiety Rating Scale (HAMA)-14, Automatic Thoughts Questionnaire (ATQ), Stigma of Mental Illness scale and Connor-Davidson Resilience Scale (CD-RISC). Serum biochemical parameters were measured by automatic biochemistry analyzer. Results: The score of ATQ was highest in the MetS group (F = 14.5, p < 0.001), and the total score of CD-RISC, subscale tenacity score and subscale strength score of CD-RISC were lowest in the MetS group (F = 8.54, p < 0.001; F = 5.79, p = 0.004; F = 10.9, p < 0.001). A stepwise regression analysis demonstrated that a negative correlation was observed among the ATQ with employment status, high-density lipoprotein (HDL-C), and CD-RISC (ß=-0.190, t=-2.297, p = 0.023; ß=-0.278, t=-3.437, p = 0.001; ß=-0.238, t=-2.904, p = 0.004). A positive correlation was observed among the ATQ with waist, TG, WBC, and stigma (ß=0.271, t = 3.340, p = 0.001; ß=0.283, t = 3.509, p = 0.001; ß=0.231, t = 2.815, p = 0.006; ß=0.251, t=-2.504, p = 0.014). The area under the receiver-operating characteristic curve analysis showed that among all independent predictors of ATQ, the TG, waist, HDL-C, CD-RISC, and stigma presented excellent specificity at 0.918, 0.852, 0.759, 0.633, and 0.605, respectively. Conclusion: Results suggested that the non-MetS and MetS groups had grievous sense of stigma, particularly, high degree of ATQ and resilience impairment was shown by the MetS group. The TG, waist, HDL-C of metabolic parameters, CD-RISC, and stigma presented excellent specificity to predict ATQ, and the waist showed excellent specificity to predict low resilience level.

Intermediary roles of prospective memory and retrospective memory in the comorbidity of depression and pain.

Background: Patients who suffer comorbidity of major depressive disorder (MDD) and chronic pain (CP) maintain a complex interplay between maladaptive prospective memory (PM) and retrospective memory (RM) with physical pain, and their complications are still unknown. Aims: We aimed to focus on the full cognitive performance and memory complaints in patients with MDD and CP, patients with depression without CP, and control subjects, considering the possible influence of depressed affect and chronic pain severity. Methods: According to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and the criteria given by the International Association of Pain, a total of 124 participants were included in this cross-sectional cohort study. Among them, 82 depressed inpatients and outpatients from Anhui Mental Health centre were divided into two groups: a comorbidity group(patients with MDD and CP) (n=40) and a depression group (patients with depression without CP) (n=42). Meanwhile, 42 healthy controls were screened from the hospital's physical examination centre from January 2019 to January 2022. The Hamilton Depression Rating Scale-24 (HAMD-24) and Beck Depression Inventory-II (BDI-II) were used to evaluate the severity of depression. The Pain Intensity Numerical Rating Scale (PI-NRS), Short-Form McGill Pain Questionnaire-2 Chinese version (SF-MPQ-2-CN), Montreal Cognitive Assessment-Basic Section (MoCA-BC), and Prospective and Retrospective Memory Questionnaire (PRMQ) were used to assess pain-related features and the global cognitive functioning of study participants. Results: The impairments in PM and RM differed remarkably among the three groups (F=7.221, p<0.001; F=7.408, p<0.001) and were severe in the comorbidity group. Spearman correlation analysis revealed the PM and RM were positively correlated with continuous pain and neuropathic pain (r=0.431, p<0.001; r=0.253, p=0.022 and r=0.415, p<0.001; r=0.247, p=0.025), respectively. Regression analysis indicated a significant positive relationship between affective descriptors and total BDI-II score (ß=0.594, t=6.600, p<0.001). Examining the mediator pathways revealed the indirect role of PM and RM in patients with comorbid MDD and CP. Conclusions: Patients with comorbid MDD and CP presented more PM and RM impairments than patients with MDD without CP. PM and RM are possibly mediating factors that affect the aetiology of comorbid MDD and CP. Trial registration number: chiCTR2000029917.

Histone deacetylase 4 inhibition ameliorates the social deficits induced by Ephrin-B2 mutation.

Deterioration of inhibitory synapse may be an essential neurological basis underlying abnormal social behaviours. Manipulations that regulate GABAergic transmission are associated with improved behavioural phenotypes in sociability. The synaptic protein, Ephrin-B2 (EB2), plays an important role in the maintenance and reconfiguration of inhibitory synapses in the medial prefrontal cortex (mPFC). However, the inhibitory cell-type specific role of EB2 in the pathophysiology and treatment of social deficits remains unknown. As expected, we revealed that tdTomato-expressing cells were only found in GABAergic neurons instead of excitatory neurons in transgenic EB2-vGATCre mice. This result indicated that depletion of EB2 would occur in those neurons, which further contribute to social deficits. In addition, specific over-expression of mPFC EB2 restored the defective social behaviour abnormalities. These results suggest that the effect of EB2 on social deficits is anatomically and cell-type specific. More importantly, the global upregulation of HDAC4 expression was found in EB2-vGATCre mice. Significant subcellular nuclear shuttling of HDAC4 in vGAT+ neurons was examined and quantified, suggesting a role of nuclear HDAC4 in mediating the mechanism underlying EB2 impairment in vGAT+ neurons. Treatment with LMK235 led to a remarkable rescue of social deficits, thus our data revealed a new domain for the potential utility of HDAC targeting agents to treat social deficits. In conclusion, these results not only revealed a novel molecular mechanism underlying the pathophysiology of social deficits, but also suggested a potential intervention avenue for the treatment of social deficits.

Childhood maltreatment increases the suicidal risk in Chinese schizophrenia patients.

Objectives: Childhood trauma might be a modifiable risk factor among adults with serious mental illness. However, the correlation of child trauma and suicide is unclear, which were cited most frequently as the biggest challenge to schizophrenia (SCZ) patients in China. We aim to study relationships between child trauma and suicide in SCZ patients of different disease stages. Methods: Ninety-one participants were included and divided into two groups, namely, first-episode group (n = 46), relapsed group (n = 45). The Positive and Negative Syndrome Scale was used to evaluate the severity of psychotic symptoms. The Beck's Suicide Intent Scale and The Nurses' Global Assessment of Suicide Risk were conducted by patient self-report to assess suicide symptom. The childhood trauma questionnaire was used to estimate severity of traumatic stress experienced during childhood. Results: Childhood trauma and different dimensions of suicide were significantly higher in the relapsed group than first-episode group (P < 0.01, respectively). BMI has a significant positive relationship with recent psychosocial stress (ß = 0.473, t = 3.521, P < 0.001) in first-episode group. As in relapsed group, BMI has a positive effect between severe mental illness and suicide ideation (ß = 0.672, t = 5.949, P < 0.001; ß = 0.909, t = 2.463, P < 0.001), Furthermore, emotional neglect presented positively related to the suicide risk and proneness to suicidal behavior (ß = 0.618, t = 5.518, P < 0.001; ß = 0.809, t = 5.356, P < 0.001). Conclusion: Relapsed group of patients had significantly more severe childhood trauma, recent psychosocial stress, suicidal risk and proneness to suicidal behavior. BMI and emotional neglect are unique predictors for different dimensions of suicide.

Potential Role of Pain Catastrophic Thinking in Comorbidity Patients of Depression and Chronic Pain.

Background: Although comorbidity of major depressive disorder (MDD) and chronic pain (CP) has been well-studied, their association with pain catastrophizing is largely elusive. This study aimed to investigate the potential effects of pain catastrophizing in patients with a comorbidity. Methods: In total, 140 participants were included in this study and divided into three groups according to the Diagnostic and Statistical Manual of Mental Disorders and the International Association for the study of pain (i.e., the comorbidity group: patients with depression with chronic pain, n = 45; depression group: patients with depression without chronic pain, n = 47; and healthy controls: n = 48). The Hamilton Depression Rating Scale (HAMD)-24 and Hamilton Anxiety Rating Scale (HAMA)-14 were used by professional psychiatrists to evaluate the severity of depression and anxiety. Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI) were conducted by patients' self-report to assess the symptom severity. The pain intensity numerical rating scale (PI-NRS) was used to assess the pain intensity. Pain Catastrophizing Scale (PCS) and Pain Anxiety Symptoms Scale (PASS) were used to estimate pain-related negative thinking. Results: The results showed that PASS and PCS scores were significantly different among the three groups. Particularly, the scores in the comorbidity group were the highest. The Pearson correlation analysis revealed a positive correlation between PCS (including the patients' helplessness, magnification, rumination, and total scores) and the severity of depression symptoms, anxiety symptoms, and pain intensity (P < 0.05). A stepwise regression analysis further demonstrated that the total PCS score, high monthly income level, and BDI score had positive impacts on PASS (P < 0.05). We also found that the total BDI score, disease course ≥1 year, and pain intensity had positive effects on PCS (P < 0.05), whereas years of education (≤ 12 years) had a negative effect on PCS (P = 0.012). In all, we have clearly demonstrated that PCS and PASS could serve as potentially predictive factors in patients suffering from comorbidity of MDD and CP. Conclusion: Our results suggested that the pain-related catastrophic thinking and anxiety were more severe in the comorbidity group than in MDD-only group and healthy group. Pain-related catastrophizing thoughts and anxiety may have potentially effects on the comorbidity of depression and chronic pain.

Exploring the link between cognitive deficit, self-esteem, alexithymia, and depressive symptom of schizophrenia.

OBJECTIVE: To the best of our knowledge, studies have been rarely conducted to assess the correlation between cognitive deficit, self-esteem, and alexithymia in the depressive symptoms of schizophrenia (SCZ). Therefore, this study aims to explore the risk factors associated with impairment of cognitive function, alexithymia, and self-esteem among a representative sample of first-episode schizophrenic patients. METHOD: We recruited 107 first-episode schizophrenic patients (48.6% male, 51.4% female, 36.94 ± 10.73 years) into the research group, according to the Diagnostic and Statistical Manual of Mental Disorders (5th edition). A total of 45 healthy people (51.1% male, 48.9% female, 32.47 ± 10.94 years) were enlisted in the healthy control group. Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Cognitive functions were estimated using the Montreal Cognitive Assessment Scale (MoCA). The feelings of respect and self-acceptance were tested using the Rosenberg Self-Esteem Scale (RSES). Emotion of identifying and describing were measured by self-report scale of Toronto Alexithymia Scale-20 (TAS-20). RESULTS: Overall cognitive impairment and alexithymia were found more serious in the patients of SCZ than the healthy group (p < .001, respectively). The patients of SCZ have higher self-esteem than the healthy group (p = .013). Total score of MoCA, ability of visual space and executive function, and delayed recall were explored had negatively correlation with alexithymia (r = -.319, p = .001; r = -.248, p = .010; r = -0.263, p = .006). Total score of RSES and depressive symptoms of PANSS had a positive correlation with alexithymia (r = .394, p = .001; r = .208, p = .032). Stepwise regression analyses have shown a positive relationship between difficulty describing feelings and depression subscale of PANSS (ß = .188, t = -2.007, p = .047) while a negative relationship between externally oriented thinking and depression subscale of PANSS (ß = -.244, t = -2.603, p = .011). A positive link correlation also was found between the total scores of TAS and RSES (ß = .372, t = 4.144, p = .001). A negative relevance was found between the total scores of TAS and scores of MoCA (ß = -.305, t = -3.348, p = .001). CONCLUSION: Overall impairment of cognitive function and alexithymia are commonly encountered in SCZ patients. Poor cognitive function, alexithymia, and high level self-esteem may be specific detective risk factors for the depressive symptoms of SCZ.

The Predictive Role of Aberrant Metabolic Parameters and Negative Automatic Thinking on the Cognitive Impairments Among Schizophrenia Patients with Metabolic Syndrome.

Purpose: The study aimed to clarify the cognitive impairments of schizophrenia with metabolic syndrome while evaluating their potential as risk factors. Patients and Methods: We recruited 153 participants and divided them into three groups according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria and the guideline standards for the prevention and treatment of dyslipidemia in Chinese adults in 2007 for metabolic syndrome, as follows: healthy control group (n = 47); nonmetabolic syndrome group (n = 58); and metabolic syndrome group (n = 48). Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale. Cognitive function and automatic thinking were estimated using the Montreal Cognitive Assessment Scale, Verbal Fluency Test, and Automatic Thoughts Questionnaire. Serum biochemical parameters were measured by automatic biochemistry analyzer. Results: One-way ANOVA analysis revealed that differential cognition impairments in schizophrenia patients compared to controls. Furthermore, results of multiple comparisons showed that more serious barriers in orientation, language fluency, and negative automatic thinking existed in the metabolic syndrome group than in the healthy and non-metabolic syndrome groups. Spearman correlation and stepwise linear regression analyses showed that psychopathological symptoms, high waist circumference, and high triglyceride were the predictive factors for negative automatic thoughts, orientation, and language fluency. Those results collectively revealed that high waist circumference, high triglyceride and negative automatic thinking had validity and effectiveness in predicting the cognitive function impairments of the metabolic syndrome group. Conclusion: The present findings strongly supported the notion that aberrant parameters of high waist circumference, high triglyceride and high negative automatic thoughts had validity and effectiveness predictive role for cognitive impairments in the schizophrenics with metabolic syndrome. The schizophrenia patients with metabolic syndrome should receive regular monitoring and adequate treatment for metabolic and psychological risk factors.

Network Association of Biochemical and Inflammatory Abnormalities With Psychiatric Symptoms in First-Episode Schizophrenia Patients.

Background: Cardiovascular disease (CVD) risk factors such as dyslipidemia and systemic aberrant inflammatory processes may occur in patients with psychotic disorders, which may cause increased mortality. The interplay between immune and metabolic markers and its contribution to the clinical symptoms of schizophrenia (SCZ) remain unclear. This study aimed to examine the association of a series of inflammatory factors, plasma biochemical indicators, and SCZ clinical symptomatology with the severity of SCZ symptoms. Methods: A total of 115 participants, including 79 first-episode drug-naïve patients with SCZ and 36 healthy controls, were enrolled in this study. Semi-structured interviews were used to collect sociodemographic data, family history of SCZ, and medical and psychiatric history. The Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS) were administered by a clinical psychiatrist to evaluate the symptom severity of patients with SCZ. Plasma inflammatory cytokines were measured by a fully automated electrochemiluminescent immunoassay (Meso Scale Discovery). Results: Blood routine, biochemical, and inflammation cytokine test results showed that the levels of white blood cell count, neutrophil count, natrium, CRP, IL-8, IL-6, IL-13, and IL-16 significantly increased in the case group than in the healthy controls (p < 0.05), whereas levels of red blood cell count, hemoglobin concentration, mean corpuscular hemoglobin concentration, total protein, albumin, total bile acid, high-density lipoprotein (HDL), apolipoprotein A1, blood urea nitrogen, kalium and IL-15 were lower than in the healthy controls (p < 0.05). Correlation network analysis results shown that the natrium, HDL and red blood cell count were the top 3 factors closely to with BPRS and PANSS related clinical symptoms among of correlation network (degree = 4). ROC curve analysis explored the IL-16, IL-8, IL-13, IL-15, natrium, and HDL had highly sensitivity and specificity to the predictive validity and effectiveness for SCZ symptoms. Conclusion: Our study revealed a complex interactive network correlation among the cardiovascular risk factors, biological immunity profiles, and psychotic symptoms in first-episode patients. Abnormal inflammatory factors and CVD risk factors had high sensitivity and specificity for predicting SCZ symptoms. Generally, our study provided novel information on the immune-related mechanisms involved in early CVD risk in patients with psychotic disorders.

Association Between Abundance of Haemophilus in the Gut Microbiota and Negative Symptoms of Schizophrenia.

Increasing evidence indicates an interaction between dysbiosis of the microbiota and the pathogenesis of schizophrenia. However, limited information is available on the specific microbial communities associated with symptoms of schizophrenia. Therefore, this study aimed to investigate gut microbiota dysbiosis and its relationship with psychopathologies in schizophrenia. We recruited 126 participants and divided them into three groups according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria-acute group (patients with acute schizophrenia), remission group (patients with schizophrenia in remission), and control group (healthy controls). Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale. Microbiota compositions, diversity and community structure were evaluated using 16S rRNA sequencing. Pearson's correlation analysis was used to evaluate the association between bacterial taxa and psychotic symptoms. The beta-diversity of microbiota composition in the acute group was distinct from that in the remission and control groups (PC1 = 21.11% vs. PC2 = 12.86%, P = 0.021). Furthermore, Pearson's correlation analysis revealed that abundance of Haemophilus was positively correlated with negative psychiatric symptoms (r = 0.303, P = 0.021), while abundance of Coprococcus was negatively correlated with negative psychiatric symptoms (r = -0.285, P = 0.025). Moreover, abundance of Haemophilus was positively correlated with cognition (r = 0.428, P = 0.009), excitement (r = 0.266, P = 0.037), and depression (r = 0.295, P = 0.020). The study findings suggest that alterations in certain gut microbiota may interfere with psychological symptoms in schizophrenia. Our results provide evidence that may help in the development of therapeutic strategies using microbial-based targets. The data that support the findings of this study have been deposited in the NCBI (https://submit.ncbi.nlm.nih.gov/) with accession number SUB9453991.

Case report of the treatment and experience of mental disorders due to chronic viral encephalitis.

Viral encephalitis is a common clinical condition. Its clinical manifestations are variable and include neurological symptoms and psychiatric abnormalities, which makes clinical diagnosis and treatment difficult. To date, there are only a few reported cases on mental symptoms of chronic viral encephalitis. We present a case of a 16-year-old male patient who was previously hospitalised and diagnosed with schizophrenia and treated with aripiprazole 15 mg/day but failed to respond. The patient was then given antiviral therapy and recovered after 2 weeks. Clinicians should be aware of the possbility that chronic mental disorders could be caused by viral encephalitis. In the future, diagnosis of chronic functional mental disorders should include viral encephalitis in the differential diagnosis.

Vitamin D supplementation improves anxiety but not depression symptoms in patients with vitamin D deficiency.

OBJECTIVE: Epidemiological evidence indicated a relationship between vitamin D (VD) and depression with anxiety, but their therapeutic relationship has not been fully elucidated. This study aimed to examine whether VD supplementation would relieve symptoms in patients with depression and anxiety with low serum 25-hydroxy VD [25(OH) D] levels. METHOD: Participants with low 25(OH)D levels were randomized to control or daily VD group and were followed up for 6 months. Serum concentrations of 25(OH) D were measured using commercial kits. Psychological symptoms were evaluated with the Hamilton Depression Rating Scale-17 (HAMD-17), Revised Social Anhedonia Scale (RSAS), Revised Physical Anhedonia scale (RPAS), and Hamilton Anxiety Rating Scale-14 (HAMA-14). The trial was listed in the trial registration (http://www.medresman.org.cn/uc/index.aspx; NTR number: ChiCTR2000030130). RESULTS: In this clinical population, no significant difference in depression symptoms was detected between VD group and control group at both baseline and at the endpoint of our study. The HAMD-17, RSAS, and RPAS scores did not change significantly between VD and control groups from baseline to endpoint (all p > .05). However, there was a significant difference in time effect of the total HAMA-14 scores between the two groups (ß [95% Cl] = -2.235 [-3.818, -0.653], p = .006). CONCLUSIONS: Vitamin D supplementation could improve the anxiety symptoms but not depressive symptoms in depressive patients with low VD level after the 6-month intervention.

Restless legs syndrome following the use of ziprasidone: a case report.

Restless legs syndrome (RLS) is a common sleep-related movement disorder characterised by an uncomfortable urge to move the legs that occurs during periods of inactivity. Although there have been many case reports on antipsychotic-induced RLS, ziprasidone has never been reported as a cause of RLS. We present a case of a female patient with schizophrenia who presented with symptoms of RLS following the administration of high doses of ziprasidone added to quetiapine and valproate. The patient's symptoms of RLS occurred following the administration and titration of ziprasidone to 160 mg, and were relieved upon reducing the dose to 120 mg/day. Other potential causative medications and differential diagnoses that could have caused similar symptoms were excluded. Clinicians should be aware of the potential for ziprasidone-induced RLS. Dopamine and serotonin interaction could be the mechanism underlying ziprasidone-induced RLS.